Chunzhang Yang, Ph.D.
Dr. Chunzhang Yang leads the Molecular and Cell Biology Program within the Neuro-Oncology Branch and broadly studies the genetic and molecular basis of brain tumors. The goal of his research is to understand the vulnerabilities of brain tumors and identify biological signatures that can then be used to generate experimental therapeutics to improve the current standard of care for patients.
His lab utilizes both traditional molecular biology techniques and preclinical models to determine the relevance of DNA repair pathway blockades and study other key pathways that could be inhibited in brain tumors to result in more cell death along with improved disease outcome and diminished therapy resistance in patients. The primary approaches Dr. Yang’s team uses are functional analysis of cancer biology, identification of actionable therapeutic targets, and develop experimental therapeutics for next step clinical application.
1) glioma, 2) chemotherapy, 3) IDH mutation, 4) neuro-oncology, 5) cancer metabolism
Within the scope of glioma research, Dr. Yang has designed a multifaceted approach to not only understand the disease biology, but also steer laboratory research to be translationally relevant. The first primary focus area within Dr. Yang’s lab includes using DNA repair inhibitors to sensitize glioma cells to radiation and chemotherapy. The goal of this work is to use multi-omic techniques with patient derived cell lines, tissue specimens and bioinformatics to shed light on the transcriptomic, metabolic and biochemical differences among glioma subtypes. Additionally, Dr. Yang has been focused on the neomorphic activity (change in the function) of the IDH enzyme, as well as its oncometabolite 2-hydroxyglutarate, regarding their impact in cancer biology and therapy vulnerabilities. Dr. Yang’s recent findings suggest that administering an FDA-approved PARP inhibitor (DNA repair inhibitor) could result in synthetic lethality in IDH-mutant glioma cells, which improves therapy response with reduced tumor expansion.
Another broad research endeavor in Dr. Yang’s laboratory is to identify the metabolic and biological vulnerabilities of IDH-mutant glioma cells to understand how these cells develop a protective shield from being maximally impacted by therapy. It has been found that NRF2, a transcription factor, could be a critical driver for survival in IDH-mutant tumors and the lab’s findings suggest that targeting NRF2 results in more profound cytotoxicity in a preclinical mouse model. Dr. Yang is also collaborating with other research groups within the branch and NCI to develop reliable IDH-mutant glioma mouse models that will be essential to study the disease and potential treatments in a preclinical setting.
Figure Legend: An illustration of the impact of IDH-mutant activity in glioma cells. Upon acquiring or harboring an IDH-mutation, cells undergo metabolic depletion which includes decreased levels of ATP, Glutathione and NAD+, which are all essential for normal cell function. Concurrently, IDH-mutant cells also produce 2-HG, that results in the inhibition of key enzymes involved in degradation of various compounds in the cell. Both processes together can result in a DNA repair deficiency in glioma cells, which can be therapeutically targeted with PARP inhibitors to result in synthetic lethality and subsequent cell death.
Selected Key Publications
- Proc Natl Acad Sci U S A. . 117(18): 9964-9972, 2020. [ Journal Article ]
- J. Natl. Cancer Inst. 111(10): 1033-1041, 2019. [ Journal Article ]
Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma.Clin. Cancer Res. 24(14): 3423-3432, 2018. [ Journal Article ]
β-Catenin signaling initiates the activation of astrocytes and its dysregulation contributes to the pathogenesis of astrocytomas.Proc Natl Acad Sci U S A. 109(18): 6963-6968, 2012. [ Journal Article ]
- N Engl J Med. 367(10): 922-930, 2012. [ Journal Article ]
Dr. Yang obtained his Ph.D. degree in neurobiology at Peking University in China immediately following a Bachelor of Science in Medicine at the same institution. Motivated by personal family members’ brain tumor diagnoses, he moved to the NIH shortly after completing his degrees to pursue a postdoctoral fellowship in the Surgical Neurology Branch under National Institutes of Neurological Disorders and Stroke. During this time, Dr. Yang led several research projects to understand the biology of neurological disease and central nervous system tumors to that may drive development of a therapeutic regimen that can be optimized for the disease. Following his postdoctoral fellowship in 2016, he joined the Neuro-Oncology Branch as an investigator and has been leading research efforts under the Molecular and Cell Biology Program since.
In addition to his research, Dr. Yang is part of several societies such as the American Association for Cancer Research and Society for Neuro-Oncology. He has also received several awards during his time here at the NIH including a Distiguished Scientist Award and Young Investigator Award during his postdoctoral research endeavors.
Honors, Awards and Leadership
Performance Award, Neuro-Oncology Branch, CCR, NCI - 2019
- Performance Award, Neuro-Oncology Branch, CCR, NCI - 2018
- Performance Award, Neuro-Oncology Branch, CCR, NCI - 2017
- Distinguished Scientist Award, Chinese Students and Scholars Association of the National Institutes of Health - 2016
- Young Investigator Award, Asian and Pacific Islander American Organization, US Department of Health and Human Services - 2015
- AACR-Aflac Scholar-in-Training Award, AACR Annual Meeting - 2014
- Scholarship for Excellence, Peking University, Neuroscience Research Institute - 2008
- Daiichi Sankyo Scholarship for Medical Student, Peking University - 2008
- Scholarship Award for Excellence, the ISN Special Neurochemistry Conference - 2008
- Scholarship Award for Excellence, International Symposium of the Society Chinese Bio-scientists in America (SCBA) - 2004
Select Societies and Initiatives
- American Association for Cancer Research (AACR)
- Society for Neuro-Oncology (SNO)
- Society of Chinese Bioscientists in America (SCBA)
|Sue Han Ph.D.||Postdoctoral Fellow (Visiting)|
|Yang Liu Ph.D.||Postdoctoral Fellow (Visiting)|
|Mingyu Qian||Special Volunteer|
Dr. Yanxin Lu (Postdoc fellow 2016-2018) conducted an oral presentation regarding her laboratory work in NOB in AACR Annual Meeting 2017.
Dr. Yang Liu (Postdoc fellow 2016- ) won the best poster award in 2018 Annual Symposium for the Society for Neuro-Oncology.
Our publication won "The Best of the AACR Journals" with a most-cited article in Cancer Research. Image taken during AACR Annual Meeting 2019.
On May 22nd, 2018, Dr. Yanxin Lu (Postdoc fellow 2016-2018) gave birth of a baby boy Ziyuan Yue (Jefferson).